The proposed experiments will examine the ionic and pharmacological mechanisms of action of acetylcholine (ACh) and norepinephrine (NE) within the cerebral cortex and thalamus. These two putative neurotransmitters have been implicated in the modulation of a number of important normal (e.g. learning and memory, sleep, attention, development) and abnormal (e.g. Alzheimer's disease, epilepsy, aging related cognitive deficits) neural functions. Information as to the ionic and pharmacological characteristics of the actions of ACh and NE in the forebrain is expected to further our understanding of their involvement in these normal and abnormal brain processes as well as making progress towards a possible pharmacological therapy of such. Investigations will be carried out using the in vitro slice technique in which high quality intracellular recordings and control over the neuronal chemical environment is possible. The ionic mechanisms of actions of ACh and NE will be examined in cerebral cortical and thalamic neurons using conventional intracellular current clamp and voltage clamp techniques. The intracellular second messengers which underlie these actions within the thalamus will also be examined. The actions of ACh and NE will be examined in the cerebral cortex because of the importance of the cortex in cognitive function, while the actions of these two agents will be examined in the thalamus because of the intimate relations of the thalamus with the cerebral cortex as well as it's central role in rhythmic generation of neural activity in the forebrain. Intracellular labeling with dye injections will be used to identify subtypes of neurons recorded so that a correlation between neuronal morphological subtype and electrophysiological as well as pharmacological properties can be made. Thalamic recordings will focus on three regions: 1) the lateral geniculate nucleus will be used as a model of thalamic relay nuclei; 2) the nucleus reticularis; and 3) the intralaminar nuclei. It is expected that an increased understanding of the actions of ACh and NE in the forebrain will substantially further our understanding of not only the function of these neurotransmitter systems in the CNS, but also how ascending systems from the brainstem and basal forebrain can influence the processing of information in the cerebral cortex and thalamus.